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Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):135-40. Epub 2005 Dec 21.

Global landscape of recent inferred Darwinian selection for Homo sapiens.

Author information

1
Department of Biological Chemistry, College of Medicine, Donald Bren School of Information and Computer Sciences, and Institute of Genomics and Bioinformatics, University of California, Irvine, CA 92697, USA.

Abstract

By using the 1.6 million single-nucleotide polymorphism (SNP) genotype data set from Perlegen Sciences [Hinds, D. A., Stuve, L. L., Nilsen, G. B., Halperin, E., Eskin, E., Ballinger, D. G., Frazer, K. A. & Cox, D. R. (2005) Science 307, 1072-1079], a probabilistic search for the landscape exhibited by positive Darwinian selection was conducted. By sorting each high-frequency allele by homozygosity, we search for the expected decay of adjacent SNP linkage disequilibrium (LD) at recently selected alleles, eliminating the need for inferring haplotype. We designate this approach the LD decay (LDD) test. By these criteria, 1.6% of Perlegen SNPs were found to exhibit the genetic architecture of selection. These results were confirmed on an independently generated data set of 1.0 million SNP genotypes (International Human Haplotype Map Phase I freeze). Simulation studies indicate that the LDD test, at the megabase scale used, effectively distinguishes selection from other causes of extensive LD, such as inversions, population bottlenecks, and admixture. The approximately 1,800 genes identified by the LDD test were clustered according to Gene Ontology (GO) categories. Based on overrepresentation analysis, several predominant biological themes are common in these selected alleles, including host-pathogen interactions, reproduction, DNA metabolism/cell cycle, protein metabolism, and neuronal function.

PMID:
16371466
PMCID:
PMC1317879
DOI:
10.1073/pnas.0509691102
[Indexed for MEDLINE]
Free PMC Article

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